Review on Antifungal Resistance Mechanisms in the Emerging Pathogen Candida auris

Abstract

Candida auris is an emerging multi-drug resistant yeast, that causes major issues regarding patient treatment and surface disinfection in hospitals. Indeed, an important proportion of C. auris strains isolated worldwide present a decreased sensitivity to multiple and sometimes even all available antifungals. Based on recent tentative breakpoints by the CDC, it appears that in the USA about 90, 30, and < 5% of isolates have been resistant to fluconazole, amphotericin B, and echinocandins, respectively. To date, this has lead to a low therapeutic success. Furthermore, C. auris is prone to cause outbreaks, especially since it can persist for weeks in a nosocomial environment and survive high-end disinfection procedures. In this review, we describe the molecular resistance mechanisms to antifungal drugs identified so far in C. auris and compare them to those previously discovered in other Candida species. Additionally, we examine the role that biofilm formation plays in the reduced antifungal sensitivity of this organism. Finally, we summarize the few insights on how this yeast survives on hospital surfaces and discuss the challenge it presents regarding nosocomial environment disinfection.

Keywords: Candida auris; MIC; antifungal resistance; biofilm; emerging pathogen; outbreaks.

Figure 1

(A) Map representing the number of isolates per outbreak since 1996. The first outbreak year is brown-colored and the latest outbreak year is in pink. Circle size is proportional to the number of isolates reported for each outbreak. Outbreak survey was performed recovering data from three main reviews (Osei Sekyere, ; Jackson et al., ; Kenters et al., 2019) and complemented by a pubmed search using the query “Candida” AND “auris” AND “outbreak” as keywords. Results were limited in time, between the 21/07/2017, the latest study in the systematic review by Osei Sekyere and the 31/08/2019, when the literature search was performed. Studies not present in the review by Osei Sekyere: (Biswal et al., ; Abdalhamid et al., ; Adams et al., ; Belkin et al., ; Chow et al., ; Desoubeaux et al., ; Lesho et al., ; Mayor, ; Parra-Giraldo et al., ; Ruiz-Gaitán et al., , ,; Sexton et al., ; Adam et al., ; Barantsevich et al., ; Escandón et al., ; Leach et al., ; O'Connor et al., ; Park et al., ; Sana et al., ; Sayeed et al., 2019). (B) MIC ranges for three antifungals measured in C. auris isolates from different outbreaks around the world. The red dotted line represents the tentative breakpoint proposed by the CDC. IPSV is an acronym for “India, Pakistan, South Africa, and Venezuela,” as strains from these countries were all analyzed in the same study. Outbreak survey was performed identically to (A). Only outbreak with >1 isolate were plotted. Studies cited by Osei Sekyere are signaled with [OS] and studies cited by Kenters et al. with [KE].